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Blood, 29 January 2009, Vol. 113, No. 5, pp. 1184-1191.
Prepublished online as a Blood First Edition Paper on October 16, 2008; DOI 10.1182/blood-2008-06-162180.


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VASCULAR BIOLOGY

Dusp-5 and Snrk-1 coordinately function during vascular development and disease

Kallal Pramanik1,*, Chang Zoon Chun1,*, Maija K. Garnaas1,*, Ganesh V. Samant1, Keguo Li1, Mark A. Horswill1, Paula E. North2, and Ramani Ramchandran1,2

1 Department of Pediatrics, Children's Research Institute (CRI) Developmental Vascular Biology Program, and 2 Department of Pediatric Pathology, Translational and Biomedical Research Center, Medical College of Wisconsin, Milwaukee

Mitogen-activated protein kinases play an integral role in several cellular processes. To regulate mitogen-activated protein kinases, cells express members of a counteracting group of proteins called phosphatases. In this study, we have identified a specific role that one member of this family of phosphatases, dual-specific phosphatase-5 (Dusp-5) plays in vascular development in vivo. We have determined that dusp-5 is expressed in angioblasts and in established vasculature and that it counteracts the function of a serine threonine kinase, Snrk-1, which also plays a functional role in angioblast development. Together, Dusp-5 and Snrk-1 control angioblast populations in the lateral plate mesoderm with Dusp-5 functioning downstream of Snrk-1. Importantly, mutations in dusp-5 and snrk-1 have been identified in affected tissues of patients with vascular anomalies, implicating the Snrk-1–Dusp-5 signaling pathway in human disease.


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C. Z. Chun, S. Kaur, G. V. Samant, L. Wang, K. Pramanik, M. K. Garnaas, K. Li, L. Field, D. Mukhopadhyay, and R. Ramchandran
Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates
Blood, January 29, 2009; 113(5): 1192 - 1199.
[Abstract] [Full Text] [PDF]



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